Glucose-stimulated upregulation of GLUT2 gene is mediated by sterol response element-binding protein-1c in the hepatocytes

Seung Soon Im, Seung Youn Kang, So Youn Kim, Ha Il Kim, Jae Woo Kim, Kyung Sup Kim, Yong Ho Ahn

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

GLUT2 is mainly expressed in the liver, β-cells of the pancreas, and the basolateral membrane of kidney proximal tubules and plays an important role in glucose homeostasis in living organisms. The transcription of the GLUT2 gene is known to be upregulated in the liver during postprandial hyperglycemic states or in type 2 diabetes. However, a molecular mechanism by which glucose activates GLUT2 gene expression is not known. In this study, we report evidence that sterol response element-binding protein (SREBP)-1c plays a key role in glucose-stimulated GLUT2 gene expression. The GLUT2 promoter reporter is activated by SREBP-1c, and the activation is inhibited by a dominant-negative form of SREBP-1c (SREBP-1c DN). Adenoviral expression of SREBP-1c DN suppressed glucose-stimulated GLUT2 mRNA level in primary hepatocytes. An electrophoretic mobility shift assay and mutational analysis of the GLUT2 promoter revealed that SREBP-1c binds to the -847-76 region of the GLUT2 promoter. Chromatin immunoprecipitation revealed that the binding of SREBP-1c to the -847-76 region was increased by glucose concentration in a dose-dependent manner. These results indicate that SREBP-1c mediates glucose-stimulated GLUT2 gene expression in hepatocytes.

Original languageEnglish (US)
Pages (from-to)1684-1691
Number of pages8
JournalDiabetes
Volume54
Issue number6
DOIs
StatePublished - Jun 1 2005

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Response Elements
Sterols
Hepatocytes
Carrier Proteins
Up-Regulation
Glucose
Genes
Gene Expression
Proximal Kidney Tubule
Chromatin Immunoprecipitation
Liver
Electrophoretic Mobility Shift Assay
Genetic Promoter Regions
Type 2 Diabetes Mellitus
Pancreas
Homeostasis
Messenger RNA
Membranes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Glucose-stimulated upregulation of GLUT2 gene is mediated by sterol response element-binding protein-1c in the hepatocytes. / Im, Seung Soon; Kang, Seung Youn; Kim, So Youn; Kim, Ha Il; Kim, Jae Woo; Kim, Kyung Sup; Ahn, Yong Ho.

In: Diabetes, Vol. 54, No. 6, 01.06.2005, p. 1684-1691.

Research output: Contribution to journalArticle

Im, Seung Soon ; Kang, Seung Youn ; Kim, So Youn ; Kim, Ha Il ; Kim, Jae Woo ; Kim, Kyung Sup ; Ahn, Yong Ho. / Glucose-stimulated upregulation of GLUT2 gene is mediated by sterol response element-binding protein-1c in the hepatocytes. In: Diabetes. 2005 ; Vol. 54, No. 6. pp. 1684-1691.
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